Diverse associations between oxidative stress and thromboxane A₂ in hypertensive glomerular injury

We examined the potential contributions of oxidative stress and thromboxane A₂ (TXA₂) to the development of regional heterogeneity in hypertensive glomerular injury using stroke-prone spontaneously hypertensive rats (SHRSP), an animal model of human essential hypertension. We also examined the effect of antioxidant treatment on the regional expression of thromboxane synthase (TXAS) mRNA using a microdissection method. Increases in the glomerular expression of TXAS mRNA were observed in the SHRSP at 15 weeks of age compared with those in the age-matched normotensive control Wistar-Kyoto (WKY) rats: 2.4-fold and 3.1-fold in the superficial and juxtamedullary glomeruli, respectively (P < 0.05). The heme oxygenase-1 mRNA expression was markedly increased (greater than eightfold, P < 0.05) in both the superficial and juxtamedullary glomeruli in the SHRSP compared with the expression in the WKY rats. In contrast to our expectations, the treatment of SHRSP with tempol (a superoxide dismutase mimetic) significantly (P < 0.05) increased the TXAS mRNA expression in the superficial glomeruli and did not improve the histological injury or albuminuria, which were both aggravated. Moreover, ozagrel (a TXAS inhibitor) had a suppressive effect on the TXAS mRNA expression and significantly (P < 0.05) improved the histological injury. These results indicated that although TXA₂ and oxidative stress are linked to each other, TXA₂ rather than oxidative stress may be a better therapeutic target to improve hypertensive glomerular injury.